The purpose of this work is to characterize the genetic changes that occur during speciation. One of our goals is to analyze the genetics of postzygotic isolation in Drosophila; we will focus on the role of meiotic drive in the evolution of postzygotic isolation. We also propose to turn to the study of prezygotic (behavioral) isolation in Drosophila; our goal is to identify and characterize the actual genes that cause behavioral isolation between species. Using genetic and molecular population genetic approaches, we will address the following questions: 1) Does meiotic drive cause the evolution of hybrid sterility? 2) What is the identity of the genes that cause hybrid sterility and hybrid meiotic drive? 3) What is the identity of the genes that cause behavioral isolation between species? 4) Do these genes, like the ones that cause postzygotic isolation, evolve rapidly between species? 5) If so, is this rapid evolution driven by positive natural selection? We will attempt to answer these questions by analysis of D. pseudoobscura Bogota-USA and D. sechellia-D. mauritiana hybrids. Our long-term goal is to understand how animal species, including humans, arise by determining the genetic causes of speciation. PUBLIC HEALTH RELEVANCE: Our goal is to understand how animal species, including humans, arise by discovering the genetic causes of speciation. This goal is relevant to NIH's mission as recent studies have shown that analysis of species hybrids provides a surprising route to discovery of functionally important genes that- despite their significance- change rapidly between populations or species.